Download Here

3/8/2011
D slipidemias
Dyslipidemias
 Understanding Lipid Metabolism
 Diagnosis and Classification Dyslipidemias
 Treatment Dyslipidemias
Understanding Lipid Metabolism
Factors affecting lipids –interaction of:
Age
Lack Physical Activity
Weight Gain
Poor Diet
Smoking
Genetics
Drugs
Comorbidities – Hypothroidism, Diabetes,
Renal Failure, Nephrotic Syndrome, Alcohol
Abuse, Liver Disease
1
3/8/2011
 Prevalence of lipid abnormalities and risk factors in
CAD
- 15% patients have no identifiable lipid disorder
- 5% patient have no risk factors for CAD
- Majority of CAD patients do have multiple risk
factors

Lipoproteins – means of transporting lipids in
circulation
- Description: core, shell, apoprotein
- Classification: chylomicrons, LDL, IPL, VLPL, HDL
- Important enzymes and transport proteins for lipid
metabolism
2
3/8/2011
Functional Division of Lipid Metabolism
 Intestinal Pathway (Exogenous)
 Hepatic Pathway (Endogenous)
 Reverse Cholesterol Pathway
3
3/8/2011
4
3/8/2011
5
3/8/2011
Diagnois and Classification Dyslipidemias
 Frederickson Classification
Types
I. Hyperchylomicronemia- very high fasting
chylomicrons and TG
II. a. Hyperbetalipoproteinemia elevated LDLC
b. Hyperbetalipoproteinemia elevated LDLC
prebetalipoproteinemia and VLDL-TG
III. Broad Betahyperlipoprotenemia elevated VLDL
remnant with ↑ cholesterol and ↑ TG
IV. Prebeta hyperlipoproteinemia and chylomicronemia
↑ chylomicrons and VLDL with high TG
Genetic and Phenotypic Disorder of Lipids
 Familial hypercholesterolemia
- Homozygous C-200-475 (very rare)
- Heterozygous C- 500-100 (1:500)
 Lp “a” disorder – very malignant lipid particle
Occurring alone or associated with other lipid problems
of metabolism
25% CAD patients have varing amounts of Lp “a”
6
3/8/2011
Atherogenic Lipid Profile (ALP)
 Most common type lipid pattern seen, in over half of
CAD patients
 Increased LDL, decreased HDL, high triglycerides
Familial Combined Hyperlipidemia
 Type II-B pattern
 High LDL-C, high VLDLC and reduced HDL-C
 Family members with similar pattern
 Pattern fluctuates with diet, age, etc.
7
3/8/2011
Type V Hyperlipidemia
Very severe elevations triglycerides due to increased
VLDL and chylomicrons
 Associated with fat rich diet, obesity, and
poorly controlled diabetes
Familial Hyperchylomicronemia
 Type I – rare
 Severe elevation triglycerides secondary to
high chylomicrons
 Due to lipoprotein lipase deficiency
 Associated with p
pancreatitis and eruptive
p
xanthomas
8
3/8/2011
Abnormalities HDL
 Tangier Disease
- Near absence HDL with yellow tonsils
 High HDL due to LCAT deficiency
- Causes “fish eye” corneal infiltrations
- Not protective
 Familial hypoalphalipoproteinemia
- Low HDL
- Associated with premature CAD and
atherosclerosis
Treatment Lipid Disorders
 Suitable laboratory evaluations
 standard lipid profile
f
Desirable
Ideal
TG
< 200
<160
HDL m/f
> 40/50
<160
LDL
<100
<70
TG
<200
<150
NON-HDL
<130
<100
9
3/8/2011
NON HDL – C
NON HDL = (LDL – C + VLDL-C) – HDL-C
Above represents Apo B particles or atherogenic lipid
particles. Use when TG > 200
Friedewald Equation
LDL C = TC – (HDLLDL-C
(HDL C) – TG/5 A
Accurate
t up tto TG 400
10
3/8/2011
Laboratory Tests for Lipid Evaluation
 Homocysteine Level
 Blood Sugar
 BUN/Creatinine/UA
 Thyroid Profile
 LFTs
 Lp “a”
 LDL Subclasses: A or B
 Berkley Heart Lab Profile (Electrophoresis)
 Lipo Med Profile (NMR imaging)
 Rarely Lipoprotein Lipase Analysis
 Rarely special genetic testing
Life Style Changes
 Diet often with weight reduction
 Exercise
 Stop smoking
 Limit alcohol
11
3/8/2011
Drug Classes and Actions
 Statins – inhibit HMG-CoA reductase, rate
limiting step in cholesterol synthesis in liver
- lower LDL-C
- raise HDL-C
- lower TG
20-50%
5-10%
5-25%
Crestor, Lipitor, Zocor, Pravachol, Fluvastatin, Livalo
Fibrates
– lower TG by ↑ LPL activity which hydrolysis TG
from VLDL
− C
Can ↓ hepatic cholesterol synthesis and ↑
excretion in bile
− ↑ HDL Thru ↑ PPAR á receptors in liver
− Reduce TG 20-50%
− Raise HD 10- 35%
− Usually lower LDL 5-20 % but can ↑ in pts with
high TG
12
3/8/2011
Cholesterol Absorption Inhibitors
 Block absorption of cholesterol in small intestine and
↑ clearance from blood to liver
 Lower LDL-C 18%
Lower TG 8 %
No effect HDL
 Ezetimibe (Zetia) “Controversial”
NICOTINIC ACID
 Decrease p
production and release VLDL from liver
and FFA release from adipocytes
Decrease LDL 5-25%
Increase HDL 15-35%
Decrease TG 20-50%
13
3/8/2011
Folic Acid, B6 , B12 :
Treatment of elevated homocysteine which
d
damages
endothelium
d th li
Choosing the Right Lipid Drugs
Goal
Choice of Drugs
Reduction LDL Cholesterol
Statins; Bile resins, Nicotinic Acid, Fibrates-unreliable
Change LDL Cholesterol Levels
Nicotinic Acid, Fibrates, Bile Resins
Elevate HDL
Nicotonic Acid, Fibrates
Reduce Triglycerides
Fibrates, Nicotinic Acid, Statins, Fish oil
Reduce Lp “a”
Nicotinic Acid
Homocysteine
Folic Acid, B6, B12
14
3/8/2011
15
3/8/2011
16
3/8/2011
17
3/8/2011
18